Keywords: alkylthio(alkoxy)propionitrile, (7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-2-yl)-acetamide, ethyl acetoacetate, 2-R-7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine, PPA, thiosemicarbazide.In recent times there has been intense investigation associated the chemistry of derivatives of 5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidines (TP) due to their wide range of biological activity. 2R-thio-TPs which have high anticancer activity are of particular interest [1][2][3][4].The most widely used method for the synthesis of derivatives of 1,3,4-thidiazolo[3,2-a]pyrimidine is the cyclocondensation of 2-amino-5-R-1,3,4-thiadiazole with ethyl acetoacetate in PPA. It is known that the reaction of nitrile-containing organic compounds with thiosemicarbazide in PPA gave 2-amino-5R-1,3,4-thiadiazoles [5-10] and that the ammonia evolved in the reaction formed ammonium polyphosphate.In the present work we have found that heating 3-alkylthio(alkoxy)propionitriles with thiosemicarbazide in PPA (95-100°C, 5-6 h) gave 2-aminothiadiazoles 2 in high yield.This method ensures the more rapid formation of 5-(β-alkylthioethyl)-2-amino-1,3,4-thiadiazole which leads to the decreasing of the reaction time (4-5 h compared with 15-20 h for known methods [11,12]) and the high yield of the end product (78-84%).When phenoxypropionitrile was used as the starting material we were unable to obtain the expected 2-amino-5-phenoxyethyl-1,3,4-thiadiazole. This is evidently connected with the instability of phenoxypropionitrile under the reaction conditions.The interaction of thiosemicarbazide with β-alkylthio(alkoxy)propionitriles 1a-f in the presence of ethyl acetoacetate in a single stage led to 2-R-7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidines 3a-f.